Radiotherapy is a well-established treatment for cancer, however pelvic radiotherapy can result in radiation proctitis, particularly after treatment of prostate or cervical cancer. In severe cases, radiation proctitis can result in the need to reduce the intensity of radiotherapy, ultimately jeopardizing the patient's prognosis for successful cancer treatment. Synedgen has developed treatments using a proprietary polymer, PAAG, to reduce radiation or chemical damage to mucosal surfaces, with particularly potent radio-mitigation activity in the gastrointestinal tract. Synedgen's non-systemic oral or enema treatments have been demonstrated to reduce local and systemic inflammation, reduce cell death and improve tissue regeneration associated with radiation-induced damage in the large and small intestines and the duodenum. The results of this proposal will demonstrate proof-of-principle efficacy for Synedgen's PAAG radiation mitigation in radiation proctitis, for radiotherapy where the tumor is distal from the mucosal surface. Plans will be developed to assess any effects of the PAAG treatment on altering tumor response to radiation. Finally, hypothesis-driven gene array assessments of PAAG-affected molecular pathways leading to the observed therapeutic mechanism will be completed. The goal is to advance a novel radiation mitigation therapy to improve patient morbidity and to allow for complete or more aggressive treatment of prostate and other cancers that are limited by radiation proctitis.